The role of TNF superfamily members in T-cell function and diseases. Michael Croft. La Jolla Institute for Allergy and Immunology. The TNF superfamily plays a critical role in T-cell function and various diseases. Four key interactions—OX40L/OX40, 4-1BBL/4-1BB, CD70/CD27, and TL1A/DR3—are discussed, highlighting their potential for therapeutic applications. These interactions regulate T-cell responses and immune cell communication, influencing inflammation, autoimmunity, and cancer. Blocking or enhancing these interactions can modulate immune responses, with successful therapies targeting TNF-TNFR interactions in autoimmune and inflammatory diseases. The TNF superfamily includes 19 ligands and 30 receptors, with several interactions being studied for their effects on CD4+ and CD8+ T cells. These interactions are expressed in a context-dependent manner, with expression levels varying based on immune activation. Signaling through these receptors activates pathways that promote cell survival, cytokine production, and immune responses. Regulatory T cells (TReg) are also influenced by these interactions, with some studies showing that engaging TNF receptors on TReg cells can enhance immune responses by suppressing TReg activity. Therapeutic strategies include blocking or enhancing these interactions to treat diseases, with some interactions being more effective than others. Studies in mouse models suggest that targeting these interactions can suppress disease in inflammatory and autoimmune conditions. However, the optimal therapeutic approach depends on the disease stage and the specific interaction targeted. In cancer, these interactions can promote antitumor immunity, with some strategies showing promise in preclinical studies. Overall, these TNF superfamily interactions are important for immune regulation and have significant therapeutic potential in various diseases.The role of TNF superfamily members in T-cell function and diseases. Michael Croft. La Jolla Institute for Allergy and Immunology. The TNF superfamily plays a critical role in T-cell function and various diseases. Four key interactions—OX40L/OX40, 4-1BBL/4-1BB, CD70/CD27, and TL1A/DR3—are discussed, highlighting their potential for therapeutic applications. These interactions regulate T-cell responses and immune cell communication, influencing inflammation, autoimmunity, and cancer. Blocking or enhancing these interactions can modulate immune responses, with successful therapies targeting TNF-TNFR interactions in autoimmune and inflammatory diseases. The TNF superfamily includes 19 ligands and 30 receptors, with several interactions being studied for their effects on CD4+ and CD8+ T cells. These interactions are expressed in a context-dependent manner, with expression levels varying based on immune activation. Signaling through these receptors activates pathways that promote cell survival, cytokine production, and immune responses. Regulatory T cells (TReg) are also influenced by these interactions, with some studies showing that engaging TNF receptors on TReg cells can enhance immune responses by suppressing TReg activity. Therapeutic strategies include blocking or enhancing these interactions to treat diseases, with some interactions being more effective than others. Studies in mouse models suggest that targeting these interactions can suppress disease in inflammatory and autoimmune conditions. However, the optimal therapeutic approach depends on the disease stage and the specific interaction targeted. In cancer, these interactions can promote antitumor immunity, with some strategies showing promise in preclinical studies. Overall, these TNF superfamily interactions are important for immune regulation and have significant therapeutic potential in various diseases.